A New Way to Replace Damaged or Missing Cells

When certain cells in our bodies are missing or nonfunctional, the only current options are to treat the symptoms with drugs or try to acquire transplants. But what if cells in our own bodies could be transformed to take on the missing functions? What if we could convert cells from other organs to function as neurons after a stroke; cardiomyocytes to address heart disease; gland cells to address endocrine diseases, or cartilaginous cells to address joint deterioration? This may be a real possibility thanks to funding from the Caltech Innovation Initiative, a philanthropically funded internal grant program designed to provide research funds to high-risk but potentially high-reward projects that could produce disruptive technologies with practical applications in the marketplace.

Working with Caltech colleague Isabelle Peter and Yong Zhu of the start-up Vivoscript, Caltech biologist Eric Davidson applied seed funds from the Caltech Innovation Initiative to test experimentally a new theory of cell-fate transformation that he and Peter codeveloped. The theory posits that cells in a living patient can be converted to work as completely different types of cells. Davidson and colleagues have transformed liver cells into cells that function like pancreatic cells, at least to the extent that they produce insulin.

The work, inspired by the group's studies of gene regulatory networks in sea urchin embryos, begins with putting suites of protein molecules called transcription factors near the cells targeted for transformation. These proteins have been engineered in a proprietary way, in collaboration with Vivoscript, so that they will be taken up by cells and will travel into the nuclei. The new proteins control cellular activity by regulating gene expression. Researchers want to be able to predict the complete suite of proteins needed to durably reproduce the gene expression — and resulting normal functions — of one kind of cell in a different original cell.

These new possibilities for therapies based on cell transformation avoid the expense and hazards associated with use of genetically transformed cells or in vitro differentiated stem cells.

If the approach is generalizable and predictable, it could answer the urgent need for a safe, inexpensive way to replace damaged or missing cells. Caltech has applied for patent protection. Davidson's next step is to demonstrate the degree to which the conversion of liver cells into pancreatic cells works.